Nuclear Medicine Physics
•
Positron Emission Tomography (PET)
Jerry Allison, Ph.D.
Department of Radiology
Medical College of Georgia
A note of thanks to
Z. J. Cao, Ph.D.
Medical College of Georgia
And
Sameer Tipnis, Ph.D.
G. Donald Frey, Ph.D.
Medical University of South Carolina
for
Sharing nuclear medicine presentation content
SPECT vs PET
PET
SPECT
(Step-and-shoot acquisition)
2015
(Simultaneous acquisition)
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
SPECT vs PET imaging
Attribute
SPECT
PET
Detection
Single s
Coincident s
99mTc, 67Ga, 111In
18F, 82Rb, 13N,
E
70 – 300 keV
511 keV
Spatial res.
 10 – 12 mm
 5 - 6 mm
Atten.Correction
No / Yes*
Yes
Radionuclides
* Possible with SPECT/CT or transmission source systems
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Three steps in PET imaging
 1. Emission of positron by radionuclide
EC ~3.3%
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Three steps in PET imaging
 2. Annihilation of positron & emission of
photon pair
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Three steps in PET imaging
 3. Coincidence detection of photon pair
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
PET image formation
t1

 t = t1 – t2
 t < 6 (to 12) ns ?
Yes

Register as a
“coincident”
event
t2
Lines of response
(LOR)
Positional information is gained
LOR is assigned by electronic coincidence circuitry
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
LORs combined to form image
Reconstructions - typically OSEM (iterative)
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
+ emitters used in PET
Proton-rich nuclei: positron emission
p  n + e+ + 
18F
9
 18O8 + e+ + 
T1/2 = 110 min
15O
8
 15N7 + e+ + 
T1/2 = 2 min
13N
7
 13C6 + e+ + 
T1/2 = 10 min
11C
6
 11B5 + e+ + 
T1/2 = 20 min
82Rb
37
 82Kr36 + e+ + 
T1/2 = 73 sec
10
Two Scientists Awarded Nobel Prize In Physics For
Neutrinos Discoveries
OCTOBER 06, 2015
NPR: Arthur McDonald of Canada and Takaaki Kajita of Japan were
awarded Nobel Prize in Physics Tuesday for discovering that
subatomic particles called neutrinos can switch from one kind to
another. NPR has more about the win and how it could change
physics in a big way.
…
Today the Nobel Prize in physics was awarded to two researchers.
Takaaki Kajita, of Japan, and Arthur McDonald, of Canada, won
for showing that particles called neutrinos have mass.
…
For neutrinos to change type, the laws of physics say they have to
have mass. But the best theories at the time predicted neutrinos
were weightless. In other words, these experiments showed the
best theories were wrong.
Cosmic Gall
by John Updike
Neutrinos
Neutrinos, they are very small.
They have no charge and have no mass
And do not interact at all.
The earth is just a silly ball
To them, through which they simply pass,
Like dustmaids down a drafty hall
Or photons through a sheet of glass.
They snub the most exquisite gas,
Ignore the most substantial wall,
Cold-shoulder steel and sounding brass,
Insult the stallion in his stall,
And, scorning barriers of class,
Infiltrate you and me! Like tall
And painless guillotines, they fall
Down through our heads into the grass.
At night, they enter at Nepal
And pierce the lover and his lass
From underneath the bed—you call
It wonderful; I call it crass.
Annihilation
e- + e + = 2 
 Energy conservation:
me- = me+ = 511 keV  E + E = 2 x 511 keV


 Momentum ( p = mv ) conservation:
pe- = pe+ = 0  p + p = 0 but p  0
 2  always in opposite directions
 The two coincident ’s are detected in PET.
13
Uncertainties in annihilation
positron scatters in
tissue to lose energy
511 keV
angle divergence
180o±0.3o (18F)
+
maximum positron range: 2.3 mm 
0.22 mm FWHM resolution limitation
18F
511 keV
14
Annihilation location  Ejection location
 The distance depends on the e+ initial
kinetic energy and medium.
Isotope
Max E
Max d
FWHM
F-18
C-11
0.64 MeV
0.96 MeV
2.3 mm
3.9 mm
.22 mm
.28 mm
O-15
1.72 MeV
6.6 mm
1.1 mm
Rb-82
3.35 MeV
16.5 mm
2.6 mm
 Shorter distance in a medium with higher
density or higher Z
15
Aside: + endpoint energy & spatial
resolution
82Rb
Emax. = 3.35 Mev
Rangerms  2.6
mm
Emax. = 0.64 Mev
Rangerms  0.2 mm
18F
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Residual momentum of e+ and e Neither positron nor electron are at complete
rest when annihilation occurs. The residual
momentum causes a small angular deviation
from 180.
 h  0.0022 × ring diameter

For D = 80 cm,
h ~ 2 mm
17
Ultimate spatial resolution in PET
The uncertainties in annihilation
(location & residual particle momentum)
determine the ultimate (limiting) spatial
resolution (~ 2 mm)
18
Coincidence Detection
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Types of coincidences
(correct LOR assigned)
True
(incorrect LOR assigned)
Scatter
Random
• True coincidences form a “true” distribution of
radioactivity
2015
• Scatter & random coincidences distort the distribution
of radioactivity, add to image noise, degrade image
quality
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Count rates
P=T+R+S
P = “Prompts” (count rate
measured by detector pair)
T = Trues
T=P-S-R
R = t R1 R2
S = Scatter
R = Randoms
• R1, R2 = singles count rates in
detectors 1 and 2
Typically, t ~ 6 – 12 ns
t = coincidence timing
window
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
A = injected activity
T  A,
R1  A,
R2  A
But, R = t R1 R2
 R  A2 !
Increasing injected activity to compensate for the size of an
obese patient not very effective! (randoms rate increases faster
than trues rate)
To improve image quality, increase the acquisition time
(therefore increasing the signal-to-noise ratio)
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Time window and random coincidence
Coincidence time window: 6 - 12 ns
 Larger window: higher count rate but
more random coincidence counts
coincidence
circuit
23
Estimating random coincidence
 Delay the coincidence time window to
acquire pure random count rate
 Two coincidence time windows separated
by 64 ns (0-12 ns and 64-76 ns)

No true events in delayed window

No scatter events in delayed window

Randoms count rate same in both windows
24
Major components of a PET scanner
 Scintillation detector rings
To convert 511 keV  photons to light photons
 PMTs
To convert the light photons to electrons and to
greatly multiply the electron number

PMTs being eliminated in some cameras: PET/MR
(avalanche photodiodes)
 Electronic circuits
To amplify, shape, manipulate and discriminate
the electrical signals
 Computers
To acquire, process, display, and store images
25
No collimators in a PET scanner
 Photon direction determined by
LOR  no collimators
 Absence of lead improves:

detection efficiency (count rate)

spatial resolution
26
Modes of PET imaging
2015
2-D (with septa):
3-D (without septa):
Coincidences between detectors
in the same or nearby ring
permitted
Coincidences between detectors
in any ring permitted
2-D imaging: high
resolution
3-D imaging: high sensitivity
(increased randoms +
scatter)
(reduces randomsNuclear
+ Medicine Physics for Radiology
Residents
Sameer Tipnis, PhD, DABR
PET systems
• Multiple rings
•~5 rings
•~35 – 60 blocks per ring
•~8 slices/ring
•Ring diameter  80 to 92 cm
• Transverse FOV  60 cm
• Axial FOV  15 - 20 cm
• Attenuation correction
• X-ray CT
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Detector materials
 BGO (Bi4Ge3O12) used by GE
 LSO (Lu2SiO5) used by Siemens
 GSO (Gd2SiO5 ) used by Philips
 LYSO (Lu2YSiO5, 9(L):1(Y)) used by all
30
Stopping power (attenuation coefficients)
511 keV
140 keV
NaI
0.32/cm
2.44/cm
BGO
0.86/cm
11.76/cm
LSO
0.81/cm
9.26/cm
GSO
0.67/cm
6.37/cm
LYSO
0.50/cm
_____________________________________________________________________________
N(x) = N e-mx
For x = 3 cm, NBGO = 7.5% (for a 3 cm thick BGO
detector, 92.5% of 511 keV photons absorbed)
31
Scintillation decay time
If time interval between detecting 2 ’s too
short  pile-up effect  reduced count rate
and artifacts
NaI
BGO
LSO
GSO
LYSO
230 ns
300 ns
40 ns
60 ns
53 ns
32
Energy resolution
Depending on both fluctuation of blue
photon number and light output
NaI
BGO
LSO
GSO
LYSO
10%
17%
12-18%
10%
12-18%
33
Detector blocks PET
20 – 30
mm
PET spatial resolution is primarily
dictated by dimensions of individual
detector elements (width ~ 4 – 6 mm)
• Each detector element optically
isolated by reflective material in
crystal cuts
• Array of 4 PMTs can determine which
detector element(s) absorbed 511 keV
photon
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Detector blocks
~300 optically independent
blocks in a PET scanner
partial cuts of each block ->
8 x 8 small crystals
4 PMTs per block.
~20,000 detection elements
R
detector
T
z
T R
A
PMT
optical
coupling
Detector blocks
 Each detection element: 4 mm (T) × 4
mm (A) × 30 (R) mm


Small tangential and axial sizes  good
spatial resolution
Large radial size  high stopping power 
high count rate
 All blocks acquire data simultaneously
 significantly increasing count rate
36
Assembly of detector blocks
1 block has 8 x 8
= 64 detectors
block 2
block 3
block 4
bucket 1
block 1
1 bucket has 4 blocks
= 256 detectors
1 ring has 16 buckets
= 4096 detectors
5 rings
37
 October 7, 2015 -- Researchers at the University of California,
Davis (UC Davis) have received a five-year, $15.5 million grant to
develop what they are calling the world's first total-body PET
scanner.




National Cancer Institute and will fund the Explorer project, led by Simon
Cherry, PhD, distinguished professor of biomedical engineering and Ramsey
Badawi, PhD, a professor of radiology.
The total-body PET scanner would image an entire body all at once, and it
would acquire images much faster or at a much lower radiation dose by
capturing almost all of the available signal from radiopharmaceuticals. … the
design would line the entire inside of the PET camera bore with multiple rings
of PET detectors.
… such a total-body PET design could reduce radiation dose by a factor of 40
or decrease scanning time from 20 minutes to 30 seconds
Cherry anticipates that the first human research subjects will be scanned in
mid-to-late 2018
http://www.auntminnie.com/index.aspx?sec
=sup&sub=mol&pag=dis&ItemID=112051
38
Advantages of PET imaging
 No collimators  higher detection
efficiency and better spatial resolution
 Detector elements (4mm x 4mm x 30mm)
 higher detection efficiency and better
spatial resolution
39
2014 PET image of the ACR phantom
7.9 mm
40
2014 SPECT image of the ACR phantom
 as
9.5 mm
31.8 mm
15.9 mm
41
Sphere diameters: 9.5, 12.7, 15.9, 19.1, 25.4, and 31.8 mm
Time-of-flight PET
 It is possible to estimate the annihilation
location from the difference in arrival times
of two  photons: d = c∙t/2.
 Because of fast speed of light (c = 30 cm/ns),
fast time resolution of detection is
required for spatial accuracy.
t2
e.g. 0.067 ns  1 cm accuracy
 No such fast scintillator yet.
t1
The currently used LYSO for ToF
PET has a time resolution of 0.585 ns
which leads to 8.8 cm accuracy.
42
Time-of-flight PET
 ToF is used to improve SNR.
 The improved SNR is used either for better
image quality or for shorter scan time.
 No additional hardware is needed except
more CPU due to the heavy computation.
0.067 ns
t2
t1
0.585 ns
t2
t1
43
Time of flight PET image of a big patient
Better resolution
with ToF!
PET Data Corrections
 Attenuation (MOST IMPORTANT
CORRECTION)

CT based
 Normalization
 Correction for variation in performance of
~20,000 individual detectors
 Random coincidences
 Delayed coincidence time window (~64 ns)
 Scattered radiation
 Modeling from transmission & emission data
 Extrapolation from tails of projections
 Dead time
 Empirical models
45
Photon attenuation within patient
 Every PET study is compensated for
attenuation.
 Correction of attenuation in PET
reconstruction needs attenuation map from
CT
 m values must be extrapolated from CT energies
(< 120 keV) to 511 keV
w/o
compensated
Attenuation Correction in PET/CT
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Attenuation Correction
Without
AC
With
AC
2015
Nuclear Medicine Physics for Radiology Residents
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Photon attenuation in PET
 High
uptake in
lungs
 High
uptake in
skin
w/o attenuation
compensation
attenuation 49
compensation
Iterative reconstruction
© Physics in Nuclear Medicine: Cherry, Sorenson and Phelps
50
LORs combined to form image
Reconstructions - typically OSEM (iterative)
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Iterative reconstruction algorithms
 One iteration at one view:




Forward project the image
Compare to acquired data
Backproject P - P0
Update the image
N1 = N0 + bpj (P - P0)
N0
P
P-P0
P0
N1
52
Iterative reconstruction algorithms
 Maximum likelihood - expectation
maximization (ML-EM)

accurate but slow convergence

Updates pixel values once after comparisons
for all views
 Ordered subset - expectation maximization
(OSEM)



Updates pixel values after comparison for a
subset of views
Number of views in subset increases as
convergence occurs
Less iterations needed to achieve same
accuracy (faster convergence)
53
Typical PET / CT imaging
(1)
(2)
512 x512 128 x128 120 kVp  511 keV
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Iterative reconstruction algorithms
© Physics in Nuclear Medicine: Cherry, Sorenson and Phelps
55
Impact of Misregistration of CT data on
Attenuation Correction
Misregistration
Proper
registration
Lateral walls of
myocardium in
the PET data,
corrected with
the lower
attenuation of
lung tissue
Lateral walls
of
myocardium
corrected with
the higher
attenuation of
heart tissue
(Ref: Attenuation correction of PET cardiac data with low-dose average CT in
PET/CT, Tinsu Pan et al, Med. Phys. 33, October 2006)
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Discovery PET/CT 710
(GE)
Biograph TruePoint PETCT
(Siemens)
Ingenuity TF PET/CT
(Philips)
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Role of FDG (Fluorodeoxyglucose)

18F-FDG
is a glucose analog
 Actively transported into cells by GLUT
(glucose transport proteins)
 Both glucose and FDG phosphorylated by
hexokinase
 Glucose-6-phosphate undergoes further
metabolism in the glucose pathway
 18F-FDG-6-phosphate does not, and
remains trapped in the cell
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Role of FDG
 Tumor cells
 increased level of GLUT-1 and GLUT-3
 higher levels of hexokinase
 highly metabolically active (high mitotic
rates)
 favor the more inefficient anaerobic
pathway adding to the already increased
glucose demands
 These combined mechanisms allow for tumor
2015
cells to absorb and retain higher levels of FDG
compared to normal tissues
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Role of FDG
 NOTE - FDG is NOT cancer specific and
will accumulate in areas with high levels
of metabolism and glycolysis
 increased uptake can be expected in
sites of:
(1) hyperactivity (muscular, nervous)
(2) active inflammation (infection, sarcoid,
arthritis, etc.)
(3) tissue repair, etc.
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Hyperactivity
High FDG uptake
in pectoralis
major after
strenuous
exercise 24 hours
prior to study
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Inadequate fasting
45 min
fasting
2015
Overnight
fasting
Nuclear Medicine Physics for Radiology Residents
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Semiquantitative PET:
Standard Uptake Value (SUV)
Defined as the ratio of activity concentrations
SUV = conc. in vol. of tissue / conc. in whole
body
SUV = (MBq/kg) / (MBq/kg)
Usually, SUV ~ 2.5 taken as cut-off between
malignant and non-malignant pathology
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
SUV in clinical studies
 Numerator: highest pixel value (SUVmax) from an
ROI

Or SUVmean
 Denominator: Activity administered/ body mass

Or lean body mass

Or body surface area
 SUV will depend on –

physiologic condition, uptake time, fasting state, etc.

Image noise, resolution, ROI definition
 Small changes in SUV need to be interpreted
2015
carefully
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Requirement for reproducible
SUV

18FDG
uptake period, scan length, scanning
range, scanning direction (e.g. head to toe)
 Patient preparation: fasting, medication
 Reconstruction parameters: slice thickness,
filters
 Region-of-interest definition (SUVmax /
SUVmean/ body mass/ lean body mass/ body
surface area)
 Consistency is the most important factor!
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Effect of uptake time
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Clinical Use of PET
Oncology
(~ 90%)
2015
Cardiac & Neuro
(~ 10%)
Nuclear Medicine Physics for Radiology Residents
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Typical oncology protocol
 Administered dose – 10 to 20 mCi FDG
 ~ 60 mins. in “quiet” room” to allow
adequate uptake and trapping, clearance
from blood
 Scanning – typically “eyes-to-thighs”
 6 to 7 “bed” positions (each ~ 15 cm FOV)
 Total scan time is ~ 30 mins. (3 mins/bed)
 With time, SUVtumor  & SUVbkg. 
2015
Nuclear Medicine Physics for Radiology Residents
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Patient dose (FDG)
 Effective dose to pt.

PET: 10 mCi (370 MBq) injection  ~ 7 mSv

CT (for AC) ~ 5 mSv

CT (Diag. / contr.) ~ 15 – 18 mSv
 Absorbed dose
2015

Organ of max. dose: bladder

10 mCi (370 MBq) injection  ~ 7 mGy
Nuclear Medicine Physics for Radiology Residents
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Personnel dose (FDG)
 2.4 mSv / hr per mCi @ 1 m, 1 hr uptake + void

Effective dose (whole body exposure)

10 mCi (370 MBq) injection  ~ 24 mSv/hr @ 1 m
 Doses lower towards pt. feet compared to torso
 Minimize time of pt. contact at injecting,
escorting to rest room, positioning for scan
 Increase distance from the pt when
communicating
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
SPECT & PET
 SPECT – 2 views from opposite sides
 Res.  collimator res., which degrades rapidly with
increasing distance from collimator face
 PET – Simultaneous acquisition
 Res.  detector width; is max in center of ring
 SPECT sensitivity ~ 0.02%
 Huge losses due to absorptive collimators
 PET sensitivity- 3D ~ 2% or higher
 High sensitivity due to coincidence detection
(electronic collimation)
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR
Advantages of PET over SPECT
• Superior spatial resolution
• Higher sensitivity
2015
Nuclear Medicine Physics for Radiology Residents
Sameer Tipnis, PhD, DABR